New concepts in gas chromatographic technology are proposed which will permit rapid and sensitive (10 to the minus 12th power g) quantitation of drugs in biological fluids. The principal objectives are to: (1) investigate methods for preparing high resolution organo-silicate coated open tubular glass capillaries, (2) perfect a dual gas chromatograph previously fabricated in the Principal Investigator's laboratory for analysis of drugs in extracts from biological fluids (no other prior clean-up), (3) evaluate the performance of the combined technology utilizing clonidine, guanethidine, hydralazine and norethindrone as test drugs and developing assay procedures for these drugs, and (4) conduct a pharmacokinetic and steady state study on clonidine in rabbit plasma in order to demonstrate the practicality of the dual gas chromatograph equipped with glass capillaries and electron capture detection. Research will continue on the preparation of organosilicates which possess a mono-layer of functional groups similar or identical to those in semi-polar (OV-210, OV-225, OV-17) and polar (poly I-110, poly A-103) gas chromatographic stationary phases. The dispersion and spreading efficiency of organosilicate/stationary phase combinations in glass capillaries will be studied by electron microscopy and their utility will be tested with clonidine, hydralazine and norethindrone isolated from plasma of orally dosed rabbits. An assay for clonidine using the new gas chromatographic technology will be completed. Clonidine in rabbit plasma from single (pharmacokinetic) and multiple (steady state) oral dosing will be studied during this period.